4c8r
From Proteopedia
(Difference between revisions)
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<StructureSection load='4c8r' size='340' side='right' caption='[[4c8r]], [[Resolution|resolution]] 2.82Å' scene=''> | <StructureSection load='4c8r' size='340' side='right' caption='[[4c8r]], [[Resolution|resolution]] 2.82Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4c8r]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C8R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C8R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c8r]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C8R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4C8R FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YT:N-(3-HYDROXYPICOLINOYL)-S-(PYRIDIN-2-YLMETHYL)-L-CYSTEINE'>6YT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YT:N-(3-HYDROXYPICOLINOYL)-S-(PYRIDIN-2-YLMETHYL)-L-CYSTEINE'>6YT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gamma-butyrobetaine_dioxygenase Gamma-butyrobetaine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.1 1.14.11.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gamma-butyrobetaine_dioxygenase Gamma-butyrobetaine dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.11.1 1.14.11.1] </span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BODG_HUMAN BODG_HUMAN]] Catalyzes the formation of L-carnitine from gamma-butyrobetaine. | [[http://www.uniprot.org/uniprot/BODG_HUMAN BODG_HUMAN]] Catalyzes the formation of L-carnitine from gamma-butyrobetaine. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Carnitine is essential for fatty acid metabolism, but is associated with both health benefits and risks, especially heart diseases. We report the identification of potent, selective and cell active inhibitors of gamma-butyrobetaine hydroxylase (BBOX), which catalyses the final step of carnitine biosynthesis in animals. A crystal structure of BBOX in complex with a lead inhibitor reveals that it binds in two modes, one of which adopts an unusual 'U-shape' conformation stabilised by inter- and intra-molecular pi-stacking interactions. Conformational changes observed on binding of the inhibitor to BBOX likely reflect those occurring in catalysis; they also rationalise the inhibition of BBOX by high levels of its substrate gamma-butyrobetaine (GBB), as observed both with isolated BBOX protein and in cellular studies. | ||
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| + | Modulating carnitine levels by targeting its biosynthesis pathway - selective inhibition of gamma-butyrobetaine hydroxylase.,Rydzik AM, Chowdhury R, Kochan GT, Williams ST, McDonough MA, Kawamura A, Schofield CJ Chem Sci. 2014 May 1;5(5):1765-1771. doi: 10.1039/C4SC00020J. PMID:26682037<ref>PMID:26682037</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4c8r" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Gamma-butyrobetaine dioxygenase]] | [[Category: Gamma-butyrobetaine dioxygenase]] | ||
| + | [[Category: Human]] | ||
[[Category: Chowdhury, R]] | [[Category: Chowdhury, R]] | ||
[[Category: Kochan, G T]] | [[Category: Kochan, G T]] | ||
Revision as of 06:55, 28 March 2018
Human gamma-butyrobetaine dioxygenase (BBOX1) in complex with Ni(II) and N-(3-hydroxypicolinoyl)-S-(pyridin-2-ylmethyl)-L-cysteine (AR692B)
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